Stewardship / Resistance Scan for Feb 14, 2018

MCR-1 in Italy, Hong Kong
Fast track for ESBL inhibitor
MDR-TB drug combo

Italian researchers identify 26 E coli isolates with MCR-1 resistance gene

Italian scientists this week reported detecting the MCR-1 colistin-resistance gene in 26 Escherichia coli isolates among more than 19,000 Enterobacteriaceae that they tested as part of surveillance efforts in Romagna in northern Italy.

Writing in the International Journal of Infectious Diseases, the researchers describe how they started a surveillance program to investigate the extent of colistin resistance in the region. Colistin is an important last-resort antibiotic for treating multidrug-resistant (MDR) infections. MCR-1 was first identified in in E coli from pigs, pork products, and humans in 2015 and has now been detected in more than 30 countries.

Among 19,053 Enterobacteriaceae isolates collected from Aug 1, 2016, through Jul 31, 2017, the team identified 90 (0.47%) that were resistant to colistin, including the 26 (0.14%) E coli isolates harboring the MCR-1 gene. The gene resides on mobile sections of DNA called plasmids and can be transferred to other pathogenic bacteria, which increases the concern.

The authors conclude, "Since the prevalence rate of carbapenem resistant Enterobacteriaceae (CRE) in some hospital wards in our area is alarming, we underline the importance of a Surveillance Program to monitor the spread of the plasmid-mediated colistin resistance genes into MDR Gram-negative bacteria."
Feb 12 Int J Infect Dis study


MCR-1 found in Hong Kong fecal samples, including from healthy people

In related news, Hong Kong researchers who analyzed more than 600 fecal samples report that they have detected 14 instances of MCR-1-positive E coli isolates, according to a study yesterday in BMC Infectious Diseases.

They included all 672 samples submitted from routine analysis from Oct 31 to Nov 25, 2016, at a regional hospital. The samples were collected from 616 patients.

They detected the 14 MCR-1-positive samples from 14 separate people by employing polymerase chain reaction testing and whole-genome sequencing (WGS). Nine of the patients were healthy people seeing a physician for routine check-ups.

All the isolates were susceptible to carbapenems, but two produced extended spectrum beta-lactamase, another indication of antibiotic resistance. WGS revealed that the isolates belonged to at least 12 different sequence types and possessed diversified plasmid replicons, virulence, and acquired antibiotic resistance genes.

The authors write that MCR-1 detection in healthy individuals "is alarming considering wide diversity and high transmissibility of mcr-1 plasmids, which potentially facilitate emergence of pan-drug-resistant bacteria in future infection."
Feb 13 BMC Infect Dis study


FDA grants Fast Track designation to novel ESBL inhibitor

Biopharmaceutical company Allecra Therapeutics today announced that the US Food and Drug Administration (FDA) granted Fast Track designation to the company for its novel extended-spectrum beta-lactamase (ESBL) inhibitor, AAI101.

AAI101 is designed to overcome the resistance of ESBL-harboring gram-negative hospital pathogens to current antibiotic therapies. According to a company press release, the Fast Track designation means a planned phase 3 trial of AAI101 combined with the antibiotic cefepime for the treatment of serious hospital-acquired infections will now begin this summer.

The FDA grants Fast Track designation to facilitate the development and expedite the review of drugs with the potential to treat a serious or life-threatening conditions and fulfill an unmet medical need.

Cefepime/AAI101 is currently in phase 2 clinical development for use in complicated urinary tract infections, complicated intra-abdominal infections, and hospital- and ventilator-acquired bacterial pneumonia.
Feb 14 Allecra Therapeutics press release


Preliminary study shows new drug combo justified for some with MDR-TB

Two new drugs available for treating multi-drug resistant tuberculosis (MDR-TB) offer hope for the disease, and the combined use of bedaquiline and delamanid are seen as a promising option, but concerns about cardiotoxicity of both drugs have kept the World Health Organization from recommending them. However, a small early trial from Doctors Without Borders scientists suggests that, under some conditions, the drug combination is justified for patients who have few treatment options.

Writing in The Lancet Infectious Diseases yesterday, the team said they analyzed 28 patients who were treated with the drug combo in 2016 in Armenia, India, and South Africa. Over 6 to 12 months, the pateints receieved 400 mg of bedaquiline once a day for 2 weeks, then 200 mg of bedaquiline three times a week plus 100 mg of delamanid twice a day.

Preliminary results show that the combination appears to be safe and can lead to high rates of culture conversion in patients who have had little treatment success in the past. One death was reported in a patient with HIV who had severe immunosuppression.

The researchers concluded that while waiting for the results of clinical trials to come in, which could take 3 years, the findings support using the combination in those who have few other treatment options. "Our data suggest that broadly withholding such access over theoretical safety concerns is no longer justifiable," the team wrote.

In a commentary on study in the same journal, three European infectious disease specialists wrote that the drugs don't appear to cause additive or synergistic cardiac effects and confirmed that the cardiac effect of bedaquiline may be lower than previously thought. They said the study confirms that, under specific conditions, the combination can be justified in some patients with few other options. The conditions include adequate expertise, monitoring capacities, access to a quality-controlled lab, and support by an expert team.
Feb 13 Lancet Infect Dis study
Feb 13 Lancet Infect Dis commentary

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